Our research objectives are to define the mechanism of intestinal lipoprotein and chylomicron synthesis during fat absorption and to manipulate the process in order to form systemic lipid particles that differ in size and composition from normal. Such studies will be performed predominantly in the rat during steady state fat absorption in order to measure the turnover of dietary lipids in the mucosa and the dynamics of incorporation into intestinal-derived lymph lipoproteins. The results of some of these rat studies will be confirmed in appropriate studies in human subjects who have undergone thoracic duct cannulation and/or portal vein and hepatic vein catheterization. The metabolic fate of lipids in experimentally altered chylomicrons will be studied by systemic injection in recipient rats. The ultimate objective of hese studies is to devise ways by which the small intestinal mucosa can be induced to produce lipoproteins that will benefcially alter human fat metabolism leading to atherosclerosis. The formation and function of lipid emulsions in the intestine following fat feeding will be studied in normal volunteers, postgastrectomy patients and in the rat. The exchage of lipids between biological lipid emulsion particles found in the intestine or chylomicrons with aqueous media will be investigated in an attempt to predict the changes that might be produced in circulating lipoproteins in order to enhance the removal of cholesterol from atheromatous blood vessels.